Non-Natural α-Amino Acids

Stereodivergent Synthesis

Synergistic Pd/Cu catalysis enables independent and precise control of Z/E and R/S configurations, providing access to all four stereoisomers of trisubstituted olefin-containing unnatural α-amino acids in a single system.

Fan, Zhibo · Cai, Hu · Zi, Weiwei

Angewandte Chemie - International Edition 2025

Specifications

Stereoisomer scope

{'zh': '4', 'en': '4'}

Advantages

All stereoisomers from one system

Palladium controls the olefin configuration while copper dictates the α-carbon stereochemistry; orthogonal catalytic cycles allow access to all four stereoisomers by choosing different catalyst combinations.

No route development needed

Users can directly obtain unnatural amino acid building blocks with the desired stereochemistry, bypassing the need to develop stereoselective routes.

Applications

• Unnatural Amino Acid Synthesis：Directly provides stereoisomers of unnatural α-amino acids with trisubstituted olefins for peptide or drug building blocks.
• Peptide Drugs：Provides configuration-controlled unnatural amino acids for designing peptide drugs with specific 3D structures.
• Stereoselective Catalysis：Demonstrates how a Pd/Cu dual catalytic system orthogonally controls two stereocenters, offering a strategy for other stereodivergent reactions.